Cascade of access to interventions to prevent HIV mother to child transmission in the metropolitan area of Rio de Janeiro, Brazil

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The

Brazilian

Journal

of

INFECTIOUS

DISEASES

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

Original

article

Cascade

of

access

to

interventions

to

prevent

HIV

mother

to

child

transmission

in

the

metropolitan

area

of

Rio

de

Janeiro,

Brazil

夽

Elaine

S. Pires

Araujo

a,c,∗

_,

_Ruth

_Khalili

_Friedman

a

_,

_Luis

_Antonio

_Bastos

_Camacho

b

_,

Monica

Derrico

a

_,

_Ronaldo

_Ismério

_Moreira

a

_,

_Guilherme

_Amaral

_Calvet

a

_,

Marília

Santini

de

Oliveira

a

_,

_Valdilea

_Gonc¸alves

_Veloso

a

_,

_José

_Henrique

_Pilotto

c,d

_,

Beatriz

Grinsztejn

a

a_Laboratório_de_Pesquisa_em_DST/AIDS,_Instituto_de_Pesquisa_Clínica_Evandro_Chagas,_Fundac¸ão_Oswaldo_Cruz_(Fiocruz),_Rio_de_Janeiro,

RJ,Brazil

b_Departamento_de_{Epidemiologia}_e_Métodos_{Quantitativos}_em_Saúde,_Escola_Nacional_de_Saúde_Publica,_Fiocruz,_Rio_de_Janeiro,_RJ,_Brazil c_Hospital_Geral_de_Nova_Iguaçu,_Serviço_de_{DST/HIV/AIDS,}_Nova_Iguaçu,_Rio_de_Janeiro,_RJ,_Brazil

d_Laboratório_de_AIDS_e_Imunologia_Molecular,_Instituto_Oswaldo_Cruz,_Fiocruz,_Rio_de_Janeiro,_RJ,_Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received26May2013 Accepted3November2013 Availableonline2January2014

Keywords: HIV

HIVverticaltransmission Antiretroviralchemoprophylaxis Cohortstudies

Brazil

a

b

s

t

r

a

c

t

Objectives:TodescribetheaccesstotheinterventionsforthepreventionofHuman Immun-odeﬁciencyVirus(HIV)mothertochildtransmissionandmothertochildtransmissionrates intheoutskirtsofRiodeJaneiro,from1999to2009.

Methods:Thisisaretrospectivecohortstudy.PreventionofHIVmothertochildtransmission interventionswereaccessedandmothertochildtransmissionrateswerecalculated. Results:Thestudypopulationisyoung(median:26years;interquartilerange:22.0–31.0),with lowmonthlyfamilyincome(40.4%uptooneBrazilianminimumwage)andschooling(62.1% lessthan8years).Only47.1%(n=469)knewtheHIVstatusoftheirpartner;ofthesewomen, 39.9%hadanHIV-seronegativepartner.Amongthe1259newbornsevaluated,accesstothe antenatal,intrapartumandpostpartumpreventionofHIVmothertochildtransmission componentsoccurredin59.2%,74.2%,and97.5%respectively;91.0%ofthenewbornswere notbreastfed.Overall52.7%ofthenewbornshavebeneﬁtedfromalltherecommended interventions.Insubsequentpregnancies(n=289),67.8%ofthenewbornsreceivedthefull packageofinterventions.TheoverallrateofHIVverticaltransmissionwas4.7%andthe highestannualrateoccurredin2005(7.4%),withnodeﬁnitetrendintheperiod.

Conclusions:AccesstothefullpackageofinterventionsforthepreventionofHIVvertical transmissionwaslow,withnosigniﬁcanttrendofimprovementovertheyears.The verti-caltransmissionratesobservedwerehigherthanthosefoundinreferenceservicesinthe municipalityofRiodeJaneiroandintherichestregionsofthecountry.

夽_This _study _was _supported _by _Brazilian _Ministry _of _Health, _PN-DST/AIDS _– _{SVS/Ministério} _da _{Saúde/BIRD/UNODC.} _Projeto

AD/BRA/03/H34.AcordodeEmpréstimoBIRD4713-BR.TC292/07.

∗ _{Corresponding}_author_at:_Laboratório_de_Pesquisa_Clinica_em_DST/AIDS,_Instituto_de_Pesquisa_Clínica_Evandro_Chagas/IPEC,_Rio_de_Janeiro,

RJ,Brazil.

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Introduction

Brazil was the ﬁrst developing country to implement a nationalprogramtopreventHIVmothertochildtransmission (PMTCT).HIVCounselingandtesting,accesstoantiretroviral therapy (ART)and infantformula tosubstitute breastfeed-inghavebeenuniversallyprovidedfree-of-charge.Although PMTCT is considered as a high priority by the Brazilian MinistryofHealth (BMH),itremains arelevantproblem in the country1 _with _a _signiﬁcant _number _of _new _pediatric

casescontinuingtooccurannually.2_In_Brazil,_between₁₉₈₀

and June 2011, 13,540 cases of vertical transmission were reported;fromJanuary2010toJune2011,457newcaseswere notiﬁed.2

In Brazil, initial studies showed a MTCT rate of 16%,3

buttherehasbeenasigniﬁcantdecreaseoverrecentyears. Inanationalmulticenterstudycovering2924children,4_the

MTCTratewas8.6%in2000and7.1%in2001,with signiﬁ-cantregionaldifferences,withlessantiretroviraluseduring pregnancy in the north and northeast regions leading to higherratesoftransmission.Studiesconductedintherecent yearsstillshowstrikingregionaldisparities,withMTCTrates of between 2.4% and 4.9% in the southern and southeast regions, the wealthiestparts ofBrazil,5–8 _and _transmission

ratesashigh as9.1and 9.9inthe northeastand northern regions.9–11

Theshortcomingsofthehealthsystemhighlyimpactthe successofinterventionsforMTCT12_and_this_is_even_more

crit-icalindevelopingcountries.Barrierstotheimplementation ofthe severalinterventionsthat arepart ofthe prevention packageforHIVMTCT(MTCT)aswellastheprogrammatic resultsobtainedvary regionallyacrossthe country.8_Rio_de

JaneirorankssecondinthenumberofreportedAIDScasesin Brazil.

Althoughit islocatedin oneofthe mostindustrialized regionsofthecountry,alargedisparitystillexistsbetween therichareasandthepoorperipheralregionssurroundingthe capitalcity.ThehighestincidenceofAIDScasesinthestate isfoundinaregion calledBaixada Fluminense,an impov-erishedareaintheoutskirtsofRiodeJaneiro,inhabitedby fourmillionmarginalizedindividualswhoareplaguedby vio-lence, poverty,social injustice,and endemicand epidemic diseases.BaixadaFluminenseintegrates13municipalitiesof whichNovaIguac¸uhasthehighestpopulationdensityand territory.13_Among_the_92,089_individuals_diagnosed_with_AIDS

inRiodeJaneiroStatebetween1982and 2012,18,903were fromBaixadaFluminense.14

This study describes the cascade of access to the rec-ommendedinterventionsforPMTCTandtheratesofMTCT amongHIV-infectedpregnantwomeninametropolitanarea ofRiodeJaneiro,Brazil.

Methodology

TheHIVFamilyCareClinic(HHFCC)operates within Hospi-talGeraldeNovaIguac¸u(HGNI),thelargest publichospital in Baixada Fluminense. HHFCC is the main referral cen-terforHIV-infectedpregnantwomenandtheirinfantsand

providesfreeaccesstoantiretrovirals(ARVs)andservicesfor the preventionofMTCT. Considering 0.59%the HIV preva-lence among womenbetween 15 and 49 years,15 _rate _that

hasbeenstablesince2004,2_and_the_number_of_stillbirths_in

2011,16 _we_estimated_{approximately}₁₃₀₀_as_the_number_of

HIVpregnantwomenassistedinRiodeJaneirointhatyear; amongthose,165(12.7%)receivedcareinHHFCC-HGNI.A ret-rospectivecohortofHIV-infectedpregnantwomenandtheir newbornswasestablishedattheHHFCC-HGNIin collabora-tionwiththeInstitutodePesquisaClinicaEvandroChagas– IPEC,Fiocruz.

Inthepresentstudy,allHIV-infectedpregnantwomenand their newborns who received care at the HHFCC between 01/01/1999and31/12/2009wereincluded.Retrospectivechart reviewusingastructuredcasereportformwasconducted.The projectwasapprovedbytheHGNI(CAAE:0005.1.316.000-07) EthicsinResearchCommittee.

Studydeﬁnitions

Recommended package of interventions for HIV PMTCT according to the timing of HIV diagnosis in the pregnant women:

(a) HIV diagnosis before and during pregnancy: antenatal antiretroviraltherapy (ART)+intrapartum IVZidovudine (ZDV)+ZDVsyrup+formulaforthenewborn;

(b) HIVdiagnosisatlabor/delivery:intrapartumIVZDV+ZDV syrup+formulaforthenewborn;

(c) HIV diagnosis during the immediate postpartum: ZDV syrup+formulaforthenewborn.

HIV-positivenewbornsweredefinedasfollows:two pos-itive HIVdiagnostic tests(usingeitherthequantificationof plasmaHIVRNA(HIVviralload)ordetectionofproviralDNA) performedbetween1and6monthsofage,withoneofthem sampledafter4monthsofage.Forthosechildrenwithouta defineddiagnosiswhowereover18monthsofage,two pos-itive serologysamplesforanti-HIV-1and-2ortwopositive rapidtestsusingdifferentmethodologieswererequired.17,18

HIV-negativenewbornsweredefinedasfollows:two neg-ativeHIVdiagnostictests(usingeitherthequantificationof plasmaHIVviralloadorthedetectionofproviralDNA)were performedbetween1and6monthsofage,withoneofthem sampledafter4monthsofage,plusanon-reactiveanti-HIV serologytestafter12monthsofage.Forthosechildrenwithout adefineddiagnosiswhowereover18monthsofage,a nonre-activeHIVserologyoranegativeresultusingtworapidtests wasrequired.Indiscordantcases,athirdtestwasconsidered toreachadiagnosticconclusion.18

HIV-inconclusivenewbornsweredeﬁnedasfollows: chil-dren who did not have one of above deﬁnitions were consideredasinconclusiveforHIVserostatus,andthereason maybeattributedtolosttofollow-uporincomplete informa-tioninmedicalcharts.

CD4+lymphocytecountatenrolment(cells/mm3_):_the_ﬁrst

resultobtainedattheentryinthecohort.

Skincolor:thiswasobtainedfromchartreviewandwas attributedbyhealthprofessionals.

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Statisticalanalyses

Frequency, mean, standard deviation (SD), median and interquartile range (IQR) were used to describe the socio-demographic,behavioralandreproductivecharacteristics,as wellasthoserelatedtoHIV/AIDSinfectionofwomenatentry inthecohort(n=997)andalsotodescribethecharacteristics ofthe pregnancieswhichresultedindeliveryinthecohort (n=1269)betweenJanuary1999andDecember2009.

Wedescribedthemunicipalityofresidenceforallwomen includedinthestudyandforthesubgroupofwomenwhodid notreceiveprenatalcareusingmapsgeneratedbyESRI2011 softwareprogramonlyforillustrativepurpose.19

Descriptivestatisticswereusedtodescribeaccessto pro-phylactic interventions to reducethe risk of perinatal HIV transmissioninthispopulation,accordingtothemomentof maternalmotherHIVdiagnosis.Trendanalysiswascarried outinordertoevaluatetheaccesstorecommendedpackage ofinterventionsaccordingtothemomentofmaternalmother HIVdiagnosisovertime.Theoverallandannualratesof peri-natalHIVtransmissionwerealsocalculated.

Results

Overall,997womenwereincludedinthecohortwithatotalof 1326pregnanciesduringthestudyperiod(1999–2009):747of thewomenhadonlyonepregnancy,188hadtwopregnancies, 46hadthreepregnancies,15hadfourpregnanciesandonehad ﬁvepregnancies.Intotal, 329subsequentpregnancieswere observedamong250women,ofwhich289resultedin live-birthinfants.

Ofall1326pregnanciesobservedinthecohort,1269(95.7%) resultedindelivery.Eighteendeliveriesweretwins,resulting inatotalof1287newborns. Ofthese,97.9% (n=1260)were live-birthinfantsforwhomthecascadeofPMTCT interven-tionswasevaluated.Losstofollow-upduringtheantenatal careperiodoccurredin0.5%ofallthepregnancies(Fig.1).

Thecharacteristicsofallwomen(n=997)attheentryinthe cohortarepresentedinTable1.Themajorityofthemresided inthemunicipalityofNovaIguac¸u(41.1%),whereHHFCCis located,followedbythemunicipalitiesofBelfordRoxo(12.4%), SãoJoãode Meriti(9.5%), Queimados(9.1%), Riode Janeiro (6.9%)andDuquedeCaxias(5.7%)(Fig.2).Themedianagewas 26years(IQR:22.0–31.0);39%ofthewomenwereyoungerthan 24yearsofage,72.9%werenon-white(Table1).Approximately 62%ofthemhadlessthan8yearsofschooling,and40.4%had afamilyincomeofuptooneBrazilianminimumwage(varied fromU$70.58toU$234.46duringthestudyperiod).

Most ofthe women (75.3%) lived with a partner atthe timeofcohortinclusion,butonly47.1%(n=469)wereaware of the partner’s HIV serostatus. An HIV-1-infected partner wasreported by60.1%,while39.9% wereinserodiscordant relationships. The mediannumber ofpregnancies prior to inclusioninthecohortwas2.0(IQR:1.0–3.0).Intotal,34.3% (n=342)ofthewomenreportedhavingatleastoneabortion priortoinclusion inthecohort. Tobacco,alcoholand illicit druguseduringpregnancywerereportedby24.0%,23.6%and 5.0%ofthewomen,respectively.Heterosexualtransmission wasthepredominantrouteofHIVinfectionacquisition;30%

Table1–Sociodemographic,clinicalandobstetric characteristicsofwomenandpregnanciesincludedin thestudy,1999–2009.

Variables n %

Characteristicsofpregnantwomen(n=997)a

Age(years) <18 43 4.3 18–24 346 34.7 25–35 515 51.7 >35 93 9.3 Skincolor White 270 27.1 Nonwhite 727 72.9 Schooling(years) <8 619 62.1 ≥8 352 35.3

Datanotavailable 26 2.6

SexualpartnerHIVserostatus

Nosexualpartner 24 2.4

Positive 282 28.3

Negative 187 18.8

Unknown 429 43.0

Numberofpreviouspregnancies

None 178 17.9

1 174 17.5

2 212 21.3

≥3 369 37.0

TimeofHIVtestingb

Beforepregnancy 199 20.0

Duringpregnancy 449 45.0

Intrapartum 177 17.8

Postpartum 171 17.2

AIDS-CDC1993

Yes 312 31.3

No 657 65.9

CD4+lymphocytecountatenrolment(cells/mm3₎

<200 75 7.5

200–350 191 19.2

>350 511 51.3

Characteristicsofprenatalanddelivery(n=1269)a

Gestationalageatthebeginningofprenatal(weeks)

Noprenatalvisits 127 10.0

<14 227 17.9

14–28 507 40.0

>28 138 10.9

Numberofprenatalvisits

None 127 10.0 1–3 241 19.0 4–6 526 41.4 ≥7 311 24.5 Unknown 64 5.0 Maternityofdelivery HGNI 960 75.7 Otherinstitution 275 21.7

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Table1(Continued)

Variables n %

Deliveryoutsidethematernity 22 1.7 Datanotavailable 12 0.9 Modeofdelivery

Electivecesarean 531 41.8

Vaginal 514 40.5

Emergencycesarean 203 16.0 Datanotavailable 21 1.7 Membranesatdelivery

Norupture 865 68.2

Rupturelessthan3h 88 6.9 Rupturebetween3–6h 81 6.4 Rupturemorethan6h 97 7.6 Rupturenotknowingtime 81 6.4 Datanotavailable 57 4.5 Gestationalageatdelivery(weeks)

<37 185 14.6

≥37 1010 79.6

Datanotavailable 74 5.8 a _Total_number_of_women_included_in_the_cohort_(n₌_997);_Total numberofpregnanciesthatresultedindeliveryinthecohort (n=1269).

b _Time_of_HIV_testing:_the_information_is_related_to_the_ﬁrst preg-nancy inthe cohort,e.g., thepregnancyat enrolmentin the cohort.

ofthewomenhadbeenpreviouslydiagnosedwithAIDS (CDC-1993)uponcohortenrolment.

ThemeanTCD4+lymphocytecountatenrolmentwas486.8

(SD:258.7)cells/mm3_;_65.8%_of_women_had_TCD4+_lymphocyte countshigherthan 350cells/mm3 (Table1).Approximately 20%ofthewomenwereawareoftheirHIVserostatuswhen theybecame pregnant.Amongthosewho wereunawareof their HIV serostatuswhen they became pregnant (n=797), 56.3% were diagnosed during prenatal care, 22.2% during deliveryand21.5%duringtheimmediatepostpartumperiod (Table1).

Thecharacteristicsofallpregnanciesthatresultedin deliv-eryinthecohort(n=1269)arepresentedinTable1.Prenatal carewasprovidedfor90%ofthesepregnancies,mostlywithin

Spontaneous abortions – N=36 (2.7%) Induced abortions – N=11 (0.8%) Ectopic pregnancy – N=3 (0.2%) Lost follow-up – N=6 (0.5%) Maternal mortality – N=1 (0.1%) Twin birth N=18 Single birth N=1,251 Stillbirths N=27 Newborns N=1,260 Births N=1,269

Children enrolled in the cohort N=1,287 Pregnancies enrolled

N=1,326

Fig.1–Studyﬂowchart.

themunicipalityofNovaIguac¸u(65.4%).Themeangestational ageatthestartofprenatalcarewas19.9(SD=7.7)weeks;in 40.0%and10.9%ofthepregnancies,prenatalcarewasinitiated between14and28weeksandafterthe28thweek,respectively. Fourormoreprenatalcarevisitsweremadein65.9%ofthe pregnancies(Table1).

ThemajorityofdeliveriesoccurredatHGNI(75.7%). Elec-tivecesareandelivery(41.8%)andvaginaldelivery(40.5%)were themostcommondeliverymethods.Spontaneousmembrane ruptureoccurredin27.3%ofthedeliveriesthatlastedlonger than3handinatleast14%ofallthedeliveries.Pretermbirths occurredin14.6%ofthepregnancies(Table1).Onehundred and thirty-sixwomen, with 157 pregnancies, didnot have accesstoanyprenatalcareinatleastonepregnancyinthe cohort.Themajorityofthemresidedinthemunicipalityof NovaIguac¸u(36.8%),followedbythemunicipalitiesofRiode

Pregnant women who did not receive antenatal care (N=136) (on at least one pregnacy while followed in the cohort)

Total of pregnant women (N=997)

Paracambi 0.0% Itaguaí 0.0% Seropédica 0.0% Rio de janeiro 12.5% Queimados 5.15% Nova lguaçu 36.8% Belford Roxo 10.3% Mesquita 5.15% Nilópolis 1.47% Rio de janeiro 6.9% Mesquita 5.1% Nilópolis 2.4% Duque de caxias 11.8% Duque de caxias 5.7% Belford Roxo 12.4% Japeri 6.62% Paracambi 0.3% Itaguai 1.2% Queimados 9.1% Nova lguaçu 41.1% Japeri 5.4% 10 5 0 10 20Km 10 5 0 10Km Seropédica 0.8%

Fig.2–Distributionofallwomen(A)andwomenwhodidnotreceiveprenatalcare(B)accordingtothemunicipalityof

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Table2–PMTCTinterventionsdeliveredtopregnantwomenandtheirnewborns,1999–2009(n=1259).

Interventionsreceivedby newborns,n(%)

TimingofHIVtesting Total Subsequentpregnancies

Beforepregnancy Duringpregnancy Labor Postpartum (n=1259)f _(n₌₂₈₉₎k,l

(n=482)e,g _(n₌₄₃₅₎h _(n₌₁₇₂₎i _(n₌₁₇₀₎j

ARVprophylaxisa₊_(IV)

ZDVb₊_formulac₊_ARV_syrupd

339(70.3) 324(74.5) – – 663(52.7) 196(67.8)

ARVprophylaxisa₊_(IV)

ZDVb₊_ARV_syrupd

8(1.7) 5(1.1) – – 13(1.0) 4(1.4)

ARVprophylaxisa₊_formulac₊_ARV

syrupd

44(9.1) 21(4.8) – – 65(5.2) 33(11.4)

ARVprophylaxisa₊_ARV_syrupd ₂_(0.4) ₃_(0.7) _– ₅_(0.4) ₁_(0.3)

(IV)ZDVb₊_Formulac₊_ARV_syrupd ₄₁_(8.5) ₆₃_(14.5) ₁₂₅_(72.7) ₂₂₉_(18.2) ₂₃_(8.0)

(IV)ZDVb₊_Formulac _– ₁_(0.2) _– _– ₁_(0.1) _–

(IV)ZDVb₊_ARV_syrupd ₁_(0.2) ₂_(0.5) ₅_(2.9) ₈_(0.6) _–

Formulac₊_ARV_syrupd ₁₄_(2.9) ₁_(0.2) ₂₃_(13.4) ₁₁₆_(68.2) ₁₅₄_(12.2) ₈_(2.8)

Onlyformulac ₁_(0.2) _– _– _– ₁_(0.1) ₁_(0.3)

OnlyARVsyrupd ₂_(0.4) ₁_(0.2) ₉_(5.2) ₄₉_(28.8) ₆₁_(4.8) ₁_(0.3)

Noneoftheinterventions 1(0.2) – – 2(1.2) 3(0.2) 1(0.3)

a _ARV_prophylaxis_–_ARV_use_during_pregnancy. b _(IV)_ZDV_–_intravenous_zidovudine.

c _Formula_–_newborns_who_were_not_breastfed_and_received_infant_formula. d_ARV_syrup_–_ARV_syrup_administered_to_newborns.

e _Among₄₈₂_newborns_who_were_born_to_women_diagnosed_with_HIV_before_pregnancy,₂₈₉_were_born_from_subsequent_pregnancies_during

thestudyperiod.

f _Of_the₁₂₆₀_newborns,_data_on_timing_of_HIV_testing_of_the_women_were_available_for_1259._Of_the₁₂₆₀_newborns,₅₃_had_missing_data_in_at

leastoneinterventionandtheydonotappearinthetable,aswecouldnotdeﬁnewhichsetofinterventionstheyreceived.

g _Of_the₄₈₂_newborns_who_were_born_to_women_diagnosed_with_HIV_before_pregnancy,₂₉_had_missing_data_in_at_least_one_intervention_and

wecouldnotdeﬁnewhichsetofinterventionstheyreceived.Amongthese29,atleast8received(IV)ZDV,14receivedformulaandatleast 17receivedARVsyrup.

h _Of_the₄₃₅_newborns_who_were_born_to_women_diagnosed_with_HIV_during_pregnancy,₁₄_had_missing_data_in_at_least_one_intervention_and

wecouldnotdeﬁnewhichsetofinterventionstheyreceived.Amongthese14,allofthemreceivedARVprophylaxis,8received(IV)ZDV,11 receivedformulaand6receivedARVsyrup.

i _Of_the₁₇₂_newborns_who_were_born_to_women_diagnosed_with_HIV_during_delivery,₁₀_had_missing_data_in_at_least_one_intervention_and_we

couldnotdeﬁnewhichsetofinterventionstheyreceived.Amongthese10,atleast4received(IV)ZDV,5receivedformulaand6receivedARV syrup.

j _Of_the₁₇₀_newborns_who_were_born_to_women_diagnosed_with_HIV_during_the_postpartum _period,₃_had_missing_data_in_at_least_one

interventionandwecouldnotdeﬁnewhichsetofinterventionstheyreceived.Amongthese3,2receivedformulaandall3receivedARV syrup.

k _Of_the₂₈₉_newborns_from_subsequent_pregnancies_in_the_cohort,₂₁_had_missing_data_in_at_least_one_intervention_and_we_could_not_deﬁne

whichsetofinterventionstheyreceived.

l _One_newborn_died_and_did_not_receive_ARV_syrup._The_death_was_related_to_prematurity_and_{hepatomegaly.}

Janeiro(12.5%),DuquedeCaxias(11.8%),SãoJoãodeMeriti (10.3%)andBelfordRoxo(10.3%)(Fig.2).

Amongallnewbornsinthecohortwithavailabledataat the timingofmaternalHIVdiagnosis (n=1259),only47.6% beneﬁtedfromtherecommendedpackageofinterventionsfor PMTCT.

The antenatal care (ANC) components of the package were usedby59.2% (n=746)ofall pregnancies(n=1259) in thiscohort.Theglobalcoverageofintrapartumintravenous zidovudine(IVZDV)componentwas74.1%(n=934),and97.5% (n=1230) ofthe newbornshad access toZDV syrup;85.5% (n=1077)wereonantiretrovirals(ARVs)syrupfor6weeks.Of those,10.1% hadnodataregardingdurationofARVssyrup exposure.Nobreastfeeding(duringtheirstayinthe mater-nityward)wasobservedin91.0%(n=1146)ofthenewborns (Table2).

Ofthenewbornswhowereborntowomendiagnosedwith HIVbeforeorduringpregnancy(n=917)andwhowould there-forehavehadtheopportunitytoreceivetheentirepackage

ofinterventionrecommendedforPMTCT,27.7%didnothave accesstoit.Approximately18%(n=138)hadnoaccesstothe antenatalcomponentofthepackageandatleast10.4%(n=95) hadnotreceivedintrapartumIVZDV.Thevastmajorityofthe newborns(95.3%)hadaccesstoinfantformula(Table2).

AmongthepregnantwomendiagnosedwithHIVduring deliveryandtheirnewborns(n=172),72.7%receivedallofthe recommendedinterventions(IVZDV,oralZDVandno breast-feeding)(Table2).Ofthenewbornswhowereborntowomen diagnosedwithHIVduringtheimmediatepostpartumperiod (n=171),only67.8%receivedtherecommendedinterventions. ARVssyrupwasusedfor6weeksby86%(n=147/171)ofthese newbornsandfor6.5%therewasnodataavailableonthe dura-tionofARVssyrupexposure.Onenewbornofamotherwhose HIVdiagnosisantedatedthecurrentpregnancyandtwo new-bornsofmothersdiagnosedwithHIVduringthepostpartum periodhavenotreceivedanyintervention(Table2).

Whenconsideringonlythesubsequentpregnanciesinthe cohort (n=289),inwhichall womenwere alreadyawareof

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9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 1999 (n=36) % 0.00.0 3.3 4.0 2.9 3.5 6.7 8.8 5.7 6.7 3.5 4.0 7.47.7 5.4 5.9 4.7 5.2 3.2 3.7 4.2 5.3 4.7 4.5 2000 (n=63) 2001 (n=72) 2002 (n=64) 2003 (n=93) 2004 (n=117) 2005 (n=160) Year 2006 (n=194) 2007 (n=201) 2008 (n=159) 2009 (n=99) Global (n=1258)

Vertical transmission rate Estimated vertical transmission rate Global and annual HIV vertical transmission rates. HGNI, 1999-2009

Fig.3–EstimatedoverallandannualMTCTrates,1999–2009.

theirHIVserostatusbeforebecomingpregnant,only67.8%of themhadaccesstotheentirepackageofinterventions recom-mendedforPMTCT;almost12%ofthemdidnothaveaccess totheantenatalcomponentsoftheinterventions(Table2).

Amongbreastfednewborns(n=91),informationon breast-feedingdurationwas availablefor62ofthem.Medianand meannumberofdaysofbreastfeedingwere1(IQR:1–2)and 5.3(SD12.6).

Regarding access to the recommended interventions according to the timing of maternal HIV diagnosis and according to the year of delivery, there was no apparent trendtowardsaccessing thecascadeofinterventionsalong the study period (before pregnancy: p=0.12; during preg-nancy:p=0.09;labor:p=0.499;postpartum:p=0.627)(datanot shown).Ofthelive-birthinfantswhosemothers were diag-nosedwithHIVatdeliveryandduringthepostpartumperiod in2009,thelastyearofinclusioninthestudy,accesstothe rec-ommendedinterventionsremainedunsatisfactory(80%and 67.7%,respectively)(datanotshown).

Theannual coverage ofIV ZDV administrationto new-bornsalsoﬂuctuatedgloballyovertheyearsandaccordingto thetimeofmaternalHIVdiagnosis.In2009,ofthelive-birth infantswhosemotherswerediagnosedwithHIVbeforeor dur-ingpregnancyandatdelivery(n=96),22.9%hadnotreceived thisintrapartumcomponent.

TheoverallrateofHIVMTCTduringthestudyperiodwas 4.7%(CI95%:3.5–5.9)(n=1258).HIVserostatuscouldnotbe determinedin223(17.9%)newborns,duetolosttofollow-up. Whenthe MTCTratewas calculatedusingthe assumption thattheHIVinfectionratewasthesameforthosenewborns inwhomanHIVdiagnosiswasnotdetermined,theestimated overalltransmissionratewas5.3%(CI95%:4.1–6.5)(Fig.3).The highestannualrateoccurredin2005(7.4%;CI95%:3.3–11.5), withnodeﬁnitetrendintheperiod(datanotshown).When consideringonlybreastfednewborns(n=91),theMTCTrate was12.1%(CI95%:5.4–18.8),signiﬁcantlyhigherthanthe3.9%

(CI95%:2.8–5.0)rateobservedamongthenon-breastfed new-borns(n=1167)(p=0.0001).

Discussion

OurresultsshowsthattheHIVMTCTratesfrom1999to2009 remainedhighamongwomenwhoreceivedANCordelivered atthismajorreferralcenterforPMTCTintheoutskirtsofRio deJaneiro.

SeveralstudiesinBrazilhavereportedtransmissionrates that are consistentwith thedata foundinour study,3,20–25

althoughlowerMTCTrateshavebeenachievedinwealthier statessuchasSãoPaulo,8 _as_a_result_of_a_better_structured

healthcaresystem.Overall,theratesfoundinBrazilarehigher thanthosereportedfromdevelopedcountries,where prophy-lacticmeasuresareimplementedearlyinpregnancyresulting inMTCTratesaround1%.26

When considering all newbornsin the cohort(n=1259), only52.7%ofthembeneﬁtedfromthecompletepackageof interventionsthatarerecommendedforPMTCT.Again,this resultissimilartothatobservedforBrazilasawhole(52%) butismuchlowerthanthatobservedinSãoPaulowherein arecentreporttherewas82%coveragefortheentire pack-ageofPMTCTinterventions.8_Despite_the_broad_knowledge_in

placeaboutthehigheffectivenessofARTduringpregnancy forPMTCT27 _and _the _universal_availability _of_ARVs_for_this

purpose inBrazil, access tothe antenatal component was observedinonly59.2%oftheﬁrstpregnanciesincludedinthis study.LatedetectionofHIVinfectionduringprenatalcare rep-resentsanopportunitytointervene,thuslimitingthenumber ofpediatriccasesasaresultofperinataltransmission.28

AccesstoHIVtesting,theentry pointforPMTCTduring antenatalcare,maybehamperedbyaseriesofevents,which result in a delayed HIV diagnosis,27,29 _leading _to _a _longer

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deliveryorpostpartum30_leads_to_unacceptably_high_risk_of

HIV transmission. The lack of HIV diagnosis during preg-nancyrepresentsonlytheﬁrst stepofacascadeofmissed opportunities. Ofnote, 26.6% ofpregnancies in which HIV infection was diagnosed before or during pregnancy have notevenreceivedoneofthecomponentsoftheprevention package.Amongthese,32.7%havenotreceivedtheantenatal component,and9.8%havereceivedtheintrapartum compo-nent.Furtherstudies are needed toidentifystrategiesand interventionstoovercomethebarriersinplaceanddecrease theinequalitiesinaccesstoPMTCTservices.

Evenmoreworrisomeistheﬁnding thatamongthe 289 subsequentpregnanciesthatresultedinlivebirthsduringthe studyperiod,only67.8%receivedthefullpackageofPMTCT interventions.Itisespeciallydisconcertingthatalmost20% ofthesesubsequentpregnancieshaveaccessedthe antena-talcomponent.Insufﬁcientlinkagetocareafterdeliveryisa well-recognizedmatteramongHIV-infectedwomen,andnot infrequentlytheysolelyresumetheircontactwiththehealth servicesatthetimeofdeliveryofasubsequentpregnancy. Lackofintegrationofhealthservices,notablybetween prena-talandmaternitycare,mayhavealsoaccountedforpartof theprobleminregardtoaccesstotheintrapartumand post-partumcomponentsofthePMTCT interventionpackage.A studyconductedinRiodeJaneirohaveindicatedthat approx-imately30%ofpregnantwomenunsuccessfullyattemptedto beadmittedto oneor morehospitals duringlabor,31 _prior

toadmissionfordelivery,highlightingthe fragileand frag-mentedhealthsysteminplace.

Breastfeedingwasobservedin9%ofthenewborns, simi-lartotheratereportedinastudy fromPernambuco,inthe NortheastregionofBrazil10_and_lower_than_the_rate_reported

inSergipe, inthe same region,11 _leading _to _a _{signiﬁcantly}

higherMTCTrateamongbreastfednewbornswhencompared tothose non-breastfed(12.1%vs.3.9%).Inacountry where formulahaslongbeenprovidedfreeofchargetoHIVinfected mothers,breastfeedingmay,infact,bemoreofamarkerof pooraccesstohealthcareingeneral.LateHIVdiagnosisofthe motherleadstoalostopportunityofadvisingagainst breast-feeding,whichisamajorfactorassociatedwithMTCT,32_and

anyexposuretobreastmilkinitselfconstitutesariskfactor fortransmission.

Several studies have conﬁrmed the strong relationship betweenthenumberofprenatalvisitsortheinitiationofearly prenatal care withsocioeconomic status and the mother’s education.27,33 _Poverty_is_a_critical_determinant_of_health_in

individualsand populations, increasingthevulnerability to severaldiseases and is amajorbarrier toaccessto health services,informationandpreventivemeasures.34_Income_and

education are strongly associatedwith health outcomes,35

andtheeffectsoftheeducationlevelareexpressedindifferent ways,such asthe perceptionofhealth problems,the abil-itytounderstandhealthinformation,theadoptionofhealthy lifestyles,theconsumptionandutilizationofhealthservices, andtheadherencetotherapeuticprocedures.HIVinfection prevalenceamongpregnantwomenandtheincidenceof ver-tical transmission have been associated with lower urban quality of residential neighborhood in Brazil.36 _Our _study

population was characterized by low income and educa-tionlevels andahigh predominanceofnon-whitewomen,

accuratelyrepresentingtheimpoverishedpopulationof Baix-adaFluminense.Despitethesignificantdecreaseinpoverty intensityduringthelastyearsinBrazil,serioussocial, eco-nomicandculturalinequitiescontinuetoplaguethecountry. These inequities include disparities related to the quality ofhealthservices, whichare fairlyevidentinprenatal ser-vicesandarestillreflectedintheinsufficienteffectiveaccess to PMTCT interventions. In order to improve engagement tocare,PMTCT programsmay needtoevaluatealternative strategiessuchasincentivesandadditionalservices, includ-ingenhancededucationonPMTCTandsexualtransmission ofHIV.Interventionsthatimprovetheengagementof preg-nantwomeninHIVcareandtreatmentprogramsareurgently neededtoachievetheWHOgoalofzeromother-to-childHIV transmission.37

Importantly, ahigh prevalence ofmultiparity (75%) and abortion(36.6%)wasobservedinthiscohort,despitethehigh proportion of women under the age of 24, indicating the insufﬁciency ofadequate family planning services suitable forthispopulation.Accordingtodatafromthe2006National HouseholdSampleSurvey(PesquisaNacionalporAmostrade Domicílios–PNAD),theoverallfertilityratein2005was2.1 childrenperwomanofchildbearingage;itrangedfromfour (forwomenwithupto3yearsofschooling)to1.5(forthose whohadeightormore38_years_of_schooling)._In_this_context,

accesstocomprehensivefamilyplanningservicestailoredto thespeciﬁcneedsoftheHIV-infectedpopulationisakey com-ponentforeffectivePMTCT.

Notably,althoughthemajorityofthewomen(75.3%)were livingwiththeirpartnersatthetimeofinclusioninthecohort, only47.1%wereawareoftheirHIVserostatus,andofthese women, 39.9%had anHIV-uninfectedsexualpartner, high-lighting thesubstantial riskforHIVsexualtransmissionin these serodiscordant relationships and the critical needto implementearlyARTinthesesituations,giventhe96% reduc-tionintheriskofHIVtransmission.39_Furthermore,_untreated

HIVinfectionhasanegativeimpactonhealththroughoutthe courseoftheinfection.40_Taken_together,_these_data_support

therevisedPMTCTrecommendationsoftheBrazilianMinistry ofHealth,whichrecommendARTpostpartummaintenance for all women who started it duringpregnancy, regardless oftheCD4cellcounts.41 _The_evidence_that_pregnancy

dou-bles theriskofHIVtransmissionfrom pregnantwomento theirpartners42_and_the_high_prevalence_of_multiparity_(75%)

observedinthisstudypopulationfurtherreiteratethis strat-egy.

Thisstudyhasseverallimitations.Asthestudywas con-ductedatasinglecenter,thestudypopulationcouldnotbe representativeofchildrenexposedtoMTCTthroughoutthe stateofRiodeJaneiro. However,thismay beoffset,asthe chosencenter,HGNI,receivesthegreatestregionaldemand forHIV-exposedchildrenintheBaixadaFluminensearea.The retrospectivenatureofourstudyhasnotallowedfor captur-ingdataonthebarrierstoPMTCTandtominimizethelostto follow-up.Asourdatawerecollectedfromclinicalrecordsand registries,thereweremissingvalues,whichwebelievehave occurred randomly.Besides,wecouldnotcollect more reli-ableimportantdataasviralload;thus,wecouldnotaccess theassociationbetweenviralloadandmodeofdeliveryand itsappropriateness.

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Theresultsfromthisstudyreﬂecttherealityoffragmented accesstoPMTCTinterventionsinBaixadaFluminense,where the municipalities with the lowest levels of development acrosstheRiodeJaneiroStatearelocated;approximately25% ofthe populationofNovaIguac¸u andDuquedeCaxiasare belowthepovertyline.

Our data provide critical insights to better understand Brazil’s low overall performance in PMTCT and may help explainsomeofthefactorsrelatedtothedisconcerting occur-renceofapproximately500casesofAIDSinchildrenunder theageofﬁveinBrazil.2_Despite_the_success_of_the_Brazilian

programforuniversalaccesstoART,thePMTCTprogramhas encounteredcriticalhurdlesrelatedtothehealthcaresystem, whichisstilldeﬁcientandmarredbyserioussocialinequities regardingaccesstoqualityhealthcare.33_In_this_context,_equal

accesstoqualiﬁedhealthservicesisessentialandwill posi-tivelyinﬂuencethecascadeofaccesstoPMTCTinterventions anddecreasethenumberofpediatricAIDScasesinBrazil.

Conﬂicts

of

interest

Theauthorsdeclarenoconﬂictsofinterest.

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1. VelosoVG,PortelaMC,VasconcellosMT,etal.HIVtesting amongpregnantwomeninBrazil:ratesandpredictors.Rev SaudePublica.2008;42:859–67.

2. Brasil,MinistériodaSaúde,SecretariadeVigilânciaemSaúde, DepartamentodeDST,AIDSeHepatitesVirais.Boletim EpidemiológicoAIDS–DST.anoVIIIn◦01;2011.Availableat: http://www.aids.gov.br/sites/default/ﬁles/anexos/publicacao/ 2011/50652/boletimaids2011ﬁnalmpdf26659.pdf [accessed06.05.13].

3. TessBH,RodriguesLC,NewellML,DunnDT,LagoTD.Infant feedingandriskofmother-to-childtransmissionofHIV-1in SaoPauloState,BrazilSaoPauloCollaborativeStudyfor VerticalTransmissionofHIV-1.JAcquirImmuneDeﬁcSyndr HumRetrovirol.1998;19:189–94.

4. SucciRCM.Mother-to-childtransmissionofHIVinBrazil duringtheyears2000and2001:resultsofamulti-centric study.CadSaudePublica.2007;23Suppl.:S379–89.

5. JoãoEC,CruzML,MenezesJA,etal.Verticaltransmissionof HIVinRiodeJaneiro,Brazil.AIDS.2003;17:1853–5.

6. KakehasiFM,PintoJA,RomanelliRM,etal.Determinantsand trendsinperinatalhumanimmunodeﬁciencyvirustype1 (HIV-1)transmissioninthemetropolitanareaofBelo Horizonte,Brazil:1998–2005.MemInstOswaldoCruz. 2008;103:351–7.

7. TornatoreM,GoncalvesCV,Mendoza-SassiRA,etal.HIV-1 verticaltransmissioninRioGrande,SouthernBrazil.IntJSTD AIDS.2010;21:351–5.

8. MatidaLH,SantosNJ,RamosJrAN,etal.Eliminatingvertical transmissionofHIVinSãoPauloBrazil:progressand challenges.JAcquirImmuneDeﬁcSyndr.2011;57 Suppl.:S164–70.

9. SoeiroCM,MirandaAE,SaraceniV,LucenaNO,TalhariS, FerreiraLC.Mother-to-childtransmissionofHIVinfectionin Manaus,StateofAmazonas,Brazil.RevSocBrasMedTrop. 2011;44:537–41.

10.GouveiaPAC,SilvaGA,AlbuquerqueMFPM.Factors associatedwithmother-to-childtransmissionofthehuman

immunodeﬁciencyvirusinPernambuco,Brazil,2000–2009. TropMedIntHealth.2013;18:276–85.

11.LemosLM,LippiJ,RutherfordGW,etal.Maternalriskfactors forHIVinfectionininfantsinnortheasternBrazil.IntJInfect Dis.2013;17:e913–8.

12.DaoH,MofensonLM,EkpiniR,etal.International recommendationsonantiretroviraldrugsfortreatmentof HIV-infectedwomenandpreventionofmother-to-childHIV transmissioninresource-limitedsettings:2006update.AmJ ObstetGynecol.2007;197Suppl.:S42–55.

13.MinistériodoPlanejamento.OrçamentoeGestão,Instituto BrasileirodeGeografiaeEstatística–IBGECensoDemográfico 2010;2010.Availableat:http://www.censo2010.ibge.gov.br/ [accessed23.09.13].

14.Brasil,MinistériodaSaúde.DATASUS.Informac¸õesdeSaúde (TABNET);2013.Availableat:http://www2.aids.gov.br/cgi/ deftohtm.exe?tabnet/rj.def[accessed15.08.13].

15.SzwarcwaldCL,SouzaJúniorPR.Estimativadaprevalênciade HIVnapopulac¸ãobrasileirade15a49anos,2004.InBrasil. MinistériodaSaúde.BoletimEpidemiológico–AIDSeDST. AnoIII,n◦1,janeiroajunhode2006;2013.Availableat:http:// bvsms.saude.gov.br/bvs/periodicos/BOLETIM2006internet.pdf [accessed15.08.13].

16.Brasil,SistemadeInformac¸ãosobreNascidosVivos(SINASC). Availableat:

http://tabnet.datasus.gov.br/cgi/sinasc/dados/novindice.htm [accessed15.08.13].

17.Brasil,MinistériodaSaúde,SecretariadeVigilânciaem Saúde,ProgramaNacionaldeDSTeAids.Recomendac¸ões paraTerapiaAntirretroviralemCrianc¸aseAdolescentes InfectadospeloHIV;2009.Availableat:

http://www.aids.gov.br/sites/default/ﬁles/consenso pediatrico.pdf[accessed05.05.13].

18.ReadJS,CommitteeonPediatricAIDS,AmericanAcademyof Pediatrics.DiagnosisofHIV-1infectioninchildrenyounger than18monthsintheUnitedStates.Pediatrics.

2007;120:e1547–62.

19.ESRI.ArcGISDesktop:Release10.Redlands,CA: EnvironmentalSystemsResearchInstitute;2011.

20.KonopkaCK,BeckST,WiggersD,daSilvaAK,DiehlFP,Santos FG.ClinicalandepidemiologicalproﬁleofHIV-infected pregnantwomeninaserviceinsouthBrazil.RevBrasGinecol Obstet.2010;32:184–90.

21.Mussi-PinhataMM,KatoCM,DuarteG,PaschoiniMC,Bettiol H,QuintanaSM.FactorsassociatedwithverticalHIV transmissionduringtwodifferenttimeperiods:theimpactof zidovudineuseonclinicalpracticeataBrazilianreference centre.IntJSTDAIDS.2003;14:818–25.

22.FernandesRC,AraujoLC,Medina-AcostaE.Preventionof verticalHIVtransmissioninCamposdosGoytacazes,Riode Janeiro,Brazil.CadSaudePublica.2005;21:1153–9.

23.MirandaAE,SoaresRA,PradoBC,MonteiroRB,FigueiredoNC. MothertochildtransmissionofHIVinVitoria,Brazil:factors associatedwithlackofHIVprevention.AIDSCare.

2005;17:721–8.

24.DalFabbroMMFJ,CunhaRV,PaniagoAMM,LindenbergASC, FreitasGMB,NogueiraSA.Prospectivestudyonthe

preventionofverticaltransmissionofHIVinCampoGrande, MatoGrossodoSul,Brazil,from1996to2001.BrazJInfect Dis.2005;9:20–7.

25.TurchiMD,DuarteLS,MartelliCMT.Mother-to-child

transmissionofHIV:riskfactorsandmissedopportunitiesfor preventionamongpregnantwomenattendinghealthservices inGoiania,GoiasState,Brazil.CadSaudePublica.2007;23 Suppl.:S390–401.

26.TownsendCL,Cortina-BorjaM,PeckhamCS,deRuiterA,Lyall H,TookeyPA.Lowratesofmother-to-childtransmissionof HIVfollowingeffectivepregnancyinterventionsintheUnited

(9)

KingdomandIreland,2000–2006.AIDS.2008;22: 973–81.

27.BarcellosC,AcostaLMW,LisboaE,BastosFI.Surveillanceof mother-to-childHIVtransmission:socioeconomicandhealth carecoverageindicators.RevSaudePublica.2009;43:1006–14. 28.SouzaJuniorPR,SzwarcwaldCL,BarbosaJuniorA,Carvalho

MF,CastilhoEA.HIVinfectionduringpregnancy:theSentinel SurveillanceProjectBrazil,2002.RevSaudePublica.

2004;38:764–72.

29.AndradeMV,NoronhaK,SinghA,RodriguesCG,Padmadas SS.AntenatalcareuseinBrazilandIndia:scale,outreachand socioeconomicinequality.HealthPlace.2012;18:942–50. 30.VelosoVG,BastosFI,PortelaMC,etal.HIVrapidtestingasa

keystrategyforpreventionofmother-to-childtransmission inBrazil.RevSaudePublica.2010;44:803–11.

31.MenezesDC,LeiteIdaC,SchrammJM,LealMC.Evaluationof antenatalperegrinationinasampleofpostpartumwomenin RiodeJaneiro,Brazil,1999/2001.CadSaudePublica.

2006;22:553–9.

32.CoutsoudisA,DabisF,FawziW,etal.Latepostnatal transmissionofHIV-1inbreast-fedchildren:anindividual patientdatameta-analysis.JInfectDis.2004;189:2154–66. 33.MinistériodoPlanejamento,Orc¸amentoeGestão,Instituto

BrasileirodeGeografiaeEstatística–IBGE,Diretoriade Pesquisas,CoordenaçãodePopulaçãoeIndicadoresSociais. EstudosePesquisas,InformaçãoDemográficae

Socioeconômica.IndicadoresSociodemográﬁcosedeSaúde noBrasil–Número25;2009.Availableat:

http://www.ibge.gov.br/home/estatistica/populacao/indic sociosaude/2009/indicsaude.pdf[accessed06.05.13].

34.FilippiV,RonsmansC,CampbellOM,etal.Maternalhealthin poorcountries:thebroadercontextandacallforaction. Lancet.2006;368:1535–41.

35.MessiasE.Incomeinequality,illiteracyrate,andlife expectancyinBrazil.AmJPublicHealth.2003;93:1294–6.

36.VieiraAC,MirandaAE,VargasPR,MacielEL.HIVprevalence inpregnantwomenandverticaltransmissioninaccordingto socioeconomicstatus,SoutheasternBrazil.RevSaude Publica.2011;45:644–51.

37.UNAIDS,Geneva,SwitzerlandCountdowntozero:globalplan towardstheeliminationofnewinfectionsamongchildrenby 2015andkeepingtheirmothersalive;2011.Availableat: http://www.unaids.org/en/media/unaids/contentassets/ documents/unaidspublication/2011/20110609JC2137 Global-Plan-Elimination-HIV-Children en.pdf[accessed13.08.13]. 38.MinistériodoPlanejamento,Orc¸amentoeGestão,Instituto

BrasileirodeGeografiaeEstatística–IBGE,Diretoriade Geociências,CoordenaçãodeRecursosNaturaiseEstudos Ambientais,CoordenaçãodeGeografia.EstudosePesquisas, InformaçãoGeográfica.IndicadoresdeDesenvolvimento Sustentável,número7;2010.Availableat:http://www.ibge. gov.br/home/geociencias/recursosnaturais/ids/ids2010.pdf [accessed06.05.13].

39.CohenMS,ChenYQ,McCauleyM,etal.PreventionofHIV-1 infectionwithearlyantiretroviraltherapy.NEnglJMed. 2011;365:493–505.

40.UNAIDS.Globalreport:UNAIDSreportontheglobalAIDS epidemic2010.Geneva,Switzerland:UnitedNations ProgrammeonHIV/AIDS;2010.Availableat:http://www. unaids.org/en/media/unaids/contentassets/documents/ unaidspublication/210/20101123 globalreporten.pdf [accessed13.05.13].

41.WorldHealthOrganization.Useofantiretroviraldrugsfor treatingpregnantwomenandpreventingHIVinfectionin infants:executivesummary;2013

http://whqlibdoc.who.int/hq/2012/WHOHIV2012.6eng.pdf [accessed13.05.13].

42.MugoNR,HeffronR,DonnellD,etal.IncreasedriskofHIV-1 transmissioninpregnancy:aprospectivestudyamong AfricanHIV-1-serodiscordantcouples.AIDS.2011;25:1887–95.